Overview of systemic therapy for advanced triple-negative breast cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Lu , ZHANG Xiaosan , WANG Fang ,  LIU Zhenzhen

Department of Breast Disease, Henan Breast Cancer Centre, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou 450000, P. R. China;

Corresponding?author：

LIU Zhenzhen, Email: zlyyliuzhenzhen0800@zzu.edu.cn

Keywords：

triple-negative breast cancer; immune checkpoint inhibitors; antibody-drug conjugates; poly ADP-ribose polymerase inhibitors; systemic therapy

DOI：

10.7507/1007-9424.202508070

Video：

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Objective To sort out the key evidence-based data and recent advances in the systemic treatment of advanced triple-negative breast cancer (TNBC), to summarize the therapeutic strategies so as to provide guidance for clinical practice. Method The key evidence and research progress on immune checkpoint inhibitors, antibody-drug conjugates (ADCs), poly ADP-ribose polymerase (PARP) inhibitors, anti-angiogenic agents, and novel microtubule inhibitors were summarized. Results The treatment landscape for advanced TNBC has shifted from chemotherapy-centric approaches to biomarker-driven, stratified precision therapy. Based on programmed cell death ligand 1 (PD-L1) expression levels, immune therapy combined with chemotherapy is prioritized. For patients with germline breast cancer gene 1/2 (gBRCA1/2) mutations, PARP inhibitors are recommended. ADCs are suggested for second-line treatment, while novel microtubule inhibitors, either alone or in combination with anti-angiogenic agents, are preferred for later-line therapy to extend patient survival. Conclusion Dynamic monitoring of molecular biomarkers such as PD-L1 and gBRCA, combined with sequential or combined “targeted–immunotherapy–ADC” regimens in a “chemotherapy-free” approach, has shown promise in improving overall survival in advanced TNBC.

Citation： ZHANG Lu, ZHANG Xiaosan, WANG Fang, LIU Zhenzhen. Overview of systemic therapy for advanced triple-negative breast cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2025, 32(11): 1399-1407. doi: 10.7507/1007-9424.202508070 Copy

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1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2. Punie K, Kurian AW, Ntalla I, et al. Unmet need for previously untreated metastatic triple-negative breast cancer: a real-world study of patients diagnosed from 2011 to 2022 in the United States. Oncologist, 2025, 30(3): oyaf034. doi: 10.1093/oncolo/oyaf034.
3. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med, 2018, 379(22): 2108-2121.
4. Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet, 2020, 396(10265): 1817-1828.
5. Cortes J, Rugo HS, Cescon DW, et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med, 2022, 387(3): 217-226.
6. Im SA, Cortes J, Cescon DW, et al. Results from the randomized KEYNOTE-355 study of pembrolizumab plus chemotherapy for Asian patients with advanced TNBC. NPJ Breast Cancer, 2024, 10(1): 79. doi: 10.1038/s41523-024-00679-7.
7. Adams S, Schmid P, Rugo HS, et al. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase Ⅱ KEYNOTE-086 study. Ann Oncol, 2019, 30(3): 397-404.
8. Emens LA, Adams S, Barrios CH, et al. First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis. Ann Oncol, 2021, 32(8): 983-993.
9. Miles D, Gligorov J, André F, et al. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase Ⅲ trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol, 2021, 32(8): 994-1004.
10. Dent R, André F, Gon?alves A, et al. IMpassion132 double-blind randomised phase Ⅲ trial of chemotherapy with or without atezolizumab for early relapsing unresectable locally advanced or metastatic triple-negative breast cancer. Ann Oncol, 2024, 35(7): 630-642.
11. Franzoi MA, de Azambuja E. Atezolizumab in metastatic triple-negative breast cancer: IMpassion130 and 131 trials—how to explain different results?. ESMO Open, 2020, 5(6): e001112. doi: 10.1136/esmoopen-2020-001112.
12. Zhang Y, Chen H, Mo H, et al. Single-cell analyses reveal key immune cell subsets associated with response to PD-L1 blockade in triple-negative breast cancer. Cancer Cell, 2021, 39(12): 1578-1593.
13. Ran R, Chen X, Yang J, et al. Immunotherapy in breast cancer: current landscape and emerging trends. Exp Hematol Oncol, 2025, 14(1): 77. doi: 10.1186/s40164-025-00667-y.
14. Bardia A, Mayer IA, Vahdat LT, et al. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med, 2019, 380(8): 741-751.
15. Jiang Z, Ouyang Q, Sun T, et al. Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: a randomized phase 3 trial. Nat Med, 2024, 30(1): 249-256.
16. Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med, 2021, 384(16): 1529-1541.
17. Rugo HS, Tolaney SM, Loirat D, et al. Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer. NPJ Breast Cancer, 2022, 8(1): 98. doi: 10.1038/s41523-022-00467-1.
18. Bardia A, Rugo HS, Tolaney SM, et al. Final results from the randomized phase Ⅲ ASCENT clinical trial in metastatic triple-negative breast cancer and association of outcomes by human epidermal growth factor receptor 2 and trophoblast cell surface antigen 2 expression. J Clin Oncol, 2024, 42(15): 1738-1744.
19. Xu B, Ma F, Wang T, et al. A phase Ⅱb, single arm, multicenter trial of sacituzumab govitecan in Chinese patients with metastatic triple-negative breast cancer who received at least two prior treatments. Int J Cancer, 2023, 152(10): 2134-2144.
20. Tolaney SM, de Azambuja E, Kalinsky K, et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1-positive advanced triple-negative breast cancer (TNBC): primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. J Clin Oncol, 2025, 43(17_suppl): LBA109. doi: 10.1200/JCO.2025.43.17_suppl.LBA109.
21. Ouyang Q, Rodon J, Liang Y, et al. Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies. J Hematol Oncol, 2025, 18(1): 61. doi: 10.1186/s13045-025-01705-2.
22. Yin Y, Fan Y, Ouyang Q, et al. Sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer: a randomized phase 3 trial. Nat Med, 2025, 31(6): 1969-1975.
23. Yin Y, Ouyang Q, Yan M, et al. Sacituzumab tirumotecan (sac-TMT) as first-line treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): initial results from the phase Ⅱ OptiTROP-Breast05 study. J Clin Oncol, 2025, 43(16_suppl): 1019. doi: 10.1200/JCO.2025.43.16_suppl.1019.
24. Bardia A, Krop IE, Kogawa T, et al. Datopotamab deruxtecan in advanced or metastatic HR⁺/HER2^– and triple-negative breast cancer: results from the phase Ⅰ TROPION-PanTumor01 Study. J Clin Oncol, 2024, 42(19): 2281-2294.
25. Dent RA, Cescon DW, Bachelot T, et al. TROPION-Breast02: Datopotamab deruxtecan for locally recurrent inoperable or metastatic triple-negative breast cancer. Future Oncol, 2023, 19(35): 2349-2359.
26. Schmid P, Wysocki PJ, Ma CX, et al. PD11-09 datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): updated results from BEGONIA, a phase 1b/2 study [abstract] // Proceedings of the 2022 San Antonio Breast Cancer Symposium, 2022 Dec 6-10, San Antonio, TX. Philadelphia (PA): AACR. Cancer Res, 2023, 83(5 Suppl): Abstract nr PD11-09. doi: 10.1158/1538-7445. SABCS22-PD11-09.
27. Schmid P, Oliveira M, O’Shaughnessy J, et al. TROPION-Breast05: a randomized phase Ⅲ study of Dato-DXd with or without durvalumab versus chemotherapy plus pembrolizumab in patients with PD-L1-high locally recurrent inoperable or metastatic triple-negative breast cancer. Ther Adv Med Oncol, 2025, 17: 17588359251327992. doi: 10.1177/17588359251327992.
28. Peiffer DS, Zhao F, Chen N, et al. Clinicopathologic characteristics and prognosis of ERBB2-low breast cancer among patients in the National Cancer Database. JAMA Oncol, 2023, 9(4): 500-510.
29. Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med, 2022, 387(1): 9-20.
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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Overview of systemic therapy for advanced triple-negative breast cancer

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